DESCRIPTION (provided by applicant): The profound fatigue experienced by patients with encephalomyelitis/chronic fatigue syndrome (ME/CFS) has led to the theory that energy metabolism may be dysregulated, but discordant results have been obtained in prior studies of mitochondrial function. Hallmark symptoms of ME/CFS) in addition to fatigue are headache, muscle aches, malaise, swollen lymph nodes, and sore throat, all characteristics of an inflammatory process. Differences between various properties of lymphocytes in ME/CFS cases and controls are well documented, but the basis of the alterations is not understood. Lymphocytes require both glycolysis and oxidative phosphorylation to carry out their immune functions. Usage of these two primary pathways for energy generation is known to change between resting and activated cells in healthy individuals. Impaired functioning of energy metabolism in lymphocytes could be either the cause or consequence of the unknown damage to cellular processes that occurs in ME/CFS. In order to investigate the efficiency and usage of glycolysis and mitochondrial respiration in ME/CFS immune cells, we will assay isolated peripheral blood mononuclear cells and isolated B, T, and NK cells with the use of a flux analyzer. We will obtain measures of basal respiration rate, maximal respiration rate, ATP synthesis rate, spare respiratory capacity, basal glycolysis rate, maximal glycolysis rate, and glycolytic reserve in immune cells before and after stimulation. We will determine whether this information correlates with any of known aspects of the proposed cohort of ME/CFS cases and controls, which will have been characterized previously for microbiome and mitochondrial DNA composition.

PUBLIC HEALTH RELEVANCE: Individuals with Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis, experience profound fatigue as well as immunological abnormalities. Both of these phenomena could result from abnormal cellular metabolism. We will perform assays to determine whether two important energy-generating pathways, oxidative phosphorylation and glycolysis, are dysregulated in lymphocytes of subjects with ME/CFS.